title: Relative free enthalpies for point mutations in two proteins with highly similar sequences but different folds.
abstract: Enveloping distribution sampling was used to calculate free-enthalpy changes associated with single amino acid mutations for a pair of proteins, GA95 and GB95, that show 95% sequence identity yet fold into topologically different structures. Of the L → A, I → F, and L → Y mutations at positions 20, 30, and 45, respectively, of the 56-residue sequence, the first and the last contribute the most to the free-enthalpy difference between the native and non-native sequence-structure combinations, in agreement with the experimental findings for this protein pair. The individual free-enthalpy changes are almost sequence-independent in the four-strand/one-helix structure, the stable form of GB95, while in the three-helix bundle structure, the stable form of GA95, an interplay between residues 20 and 45 is observed.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology , ETH, CH-8093 Zürich, Switzerland.
authors.forename: Niels
authors.initials: N
authors.lastname: Hansen
authors.forename: Jane R
authors.initials: JR
authors.lastname: Allison
authors.forename: Florian H
authors.initials: FH
authors.lastname: Hodel
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D017354:Point Mutation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins